Stanford scientists identify on/off sociability switch in brain

The release of a single signaling chemical from a specific nerve-cell tract in a particular part of the brain, like an on/off switch, may spell the difference between sociability and social awkwardness.

New drugs that can boost that chemical release’s strength or effectiveness could someday mitigate the the profound uneasiness during social interactions experienced commonly by people with autism spectrum disorder (and, occasionally, by all the rest of us).

The chemical, serotonin, is involved in other neuropsychiatric disorders such as depression. A new study in Nature conducted by Stanford neuroscientist Rob Malenka, MD, PhD, and his colleagues has shown that cranking up serotonin release from nerve cells terminating in a midbrain structure called the nucleus accumbens reliably boosts sociability in normal mice as well as other mouse mimics of the social deficits that characterize autism in humans. (Putting a lid on serotonin release has exactly the opposite effect, the study showed.)

Mice aren’t little human beings. We can’t ask them how they’re feeling about their social lives. But they provide insights into the human brain. They can be very useful for studying relatively primitive mechanisms governing social behavior. For example, if something makes a mouse want to spend more time with its buddies, that something is likely to be fun for the mouse.

Malenka is world-renowned for his decades of meticulous research in, among other things, unraveling the workings of our brain’s so-called reward circuitry: a collection of brain areas whose networked activity makes us feel good about something we’ve done or are doing. This, in turn, instructs us to do more of it.

The nucleus accumbens, found in all mammals, is a crucial hub of that circuitry.

“Evolution has ensured that certain behaviors important for survival — eating, finding a mate, procreating, successfully escaping from predators or captivity — feel great,” Malenka told me in a recent interview. In most mammals, social interaction sets off the reward circuitry, too. From the release:

‘Hanging out with your buddies makes sense from an evolutionary survival standpoint,’ Malenka said. ‘You’re more likely to find a mate and less likely to be attacked.’ But people with autism spectrum disorder don’t appear to experience the same rewarding sensation that people without these illnesses do.

The new findings give researchers added clarity in their efforts to pinpoint ways of easing the discomfort of people with autism spectrum disease when faced with the need to socialize, without causing all kinds of side effects such as addictive behaviors.

There are drugs called selective serotonin reuptake inhibitors, or SSRIs, that increase overall serotonin levels in the brain. But SSRIs, which are in wide use as antidepressants, haven’t shown an ability to counter the autism spectrum disorder’s social deficits.

“SSRIs increase serotonin levels about as much as a moderately leaky faucet,” Malenka said. “What we did in this series of experiments in mice was more like turning on that faucet to maximum flow.”